The Potential Value Of LncPARP1 In The Diagnosis And Treatment Of Hepatocellular Carcinoma

?Background?The liver plays a critical role in the human body.The functions of liver are bile secretion,metabolism,blood coagulation synthesis,detoxification,immune function,etc.Among the liver diseases,primary liver cancer causes great harm to the human society.Primary liver cancer is a common malignant tumor.The pathological types include HCC,intrahepatic bile duct carcinoma,hybrid liver cancer.HCC accounts for 90%of liver cancer.In our country,the morbidity and mortality of HCC is very high,the prognosis is poor.At present,the treatments of liver cancer that we take are comprehensive,including surgery,TACE,ablation,radiation and chemotherapy,targeted therapy,supporting treatment and so on,but the overall effect is not ideal.Recently,with the idea of ERAS and the advancements of surgical skills,the patients can recover faster and better after surgery,but the overall survival rate is still poor.Therefore,it becomes very important to seek a new method of treatment and a new target.With more and more researches of HCC made,the functions of long noncoding RNA(IncRNA)in HCC attract people's attention.LncRNA is defined as a kind of RNA without protein-coding function,and the length is greater than 200 nucleotides.Currently,researches suggest that IncRNAs involve in various aspects of gene regulation,including epigenetic modification,transcriptional regulation,post-transcriptional modifications,post-translation regulation and so on.But so far,the the specific mechanism of IncRNA in hepatocellular carcinoma(HCC)is still unknow.Combined with our previous studies,we use microarray to screen a differentially expressed IncRNA between tumor tissue and paratumor tissue.And we further study on it's functions,mechanisms and clinical significances.Then,we look forward to provide a new method for diagnosis and treatment of HCC.?Aims?The purpose of our study is to screen a IncRNA differentially expressed between cancerous and adjacent cancerous tissues,termed LncPARP1,and then,to investigate the clinical significance and its effect on the development of HCC.So,we can rich the researches of IncRNA in HCC,and wo hope to find a new target for diagnosis and treatment in HCC.[Methods]1.We use RT-PCR to detect the expression of LncPARP1 between tumor tissue and paratumor tissue from 70 HCC patients and analyze its clinical pathological datas and prognosis.2.We use lentivirus shRNA expressing system to construct stable HCC cell lines with LncPARP1 knockdown.Then,we determine the functions of LncPARP1 in HCC malignant phenotypes by using CCK-8,colony formation,apoptosis,cell cycle,transwell and subcutaneous xenografting assays.3.We use RT-PCR,Western Blot,Immunohistochemistry to analysis the correlation between LncPARP1 and PARP1.[Results]1.The expression of LncPARP1 in tumor tissues is significantly higher than that in paratumor tissues.The abnormal expression of LncPARP1 is associated with age,AFP,tumor size,postoperative recurrence(2 years)and poor prognosis.2.In vitro experiment,LncPARPl knockdown significantly inhibits cell proliferation,migration and invasion,and promotes cell apoptosis,but LncPARP1 has no effect on cell cycle.Then in vivo,subcutaneous xenografting assays show that LncPARP1 silence suppresses tumor growth,proliferation ability.3.PARP1 is the target gene of LncPARP1.The expression of PARP1 is positively correlated with LncPARP1 in vitro and vivo experiments.[Conclusions]1.LncPARP1 is high expressed in HCC and it's abnormal expression was associated with the clinical pathological characteristics and poor prognosis of HCC patients.2.Knockdown the expression of LncPARP1 can significantly inhibit cell growth and metastasis,which suggests that LncPARP1 plays oncogenic functions.3.Knockdown the expression of LncPARP1 can inhibit the expression of PARP1,which suggests that PARP1 is the target gene of LncPARP1.